The proposed Mayo Alzheimer's Disease Research Center (ADRC) will build upon the experience of the previously funded Mayo Alzheimer's Disease Center (P30) and the new faculty at Mayo Jacksonville, FL and the Mayo Scottsdale, AZ to address research questions in aging and Alzheimer's disease (AD). The ADRC will consist of five cores: Administrative Core, Clinical and Research Support Core, Neuropathology and Genetics Core, Neuroimaging Core and Education and Information Transfer Core, and two projects: Project 1: "Cytoskeletal Pathology in the Neurodegeneration of AD,"Project "The contribution of Leukoaraisosis to Cognitive Impairment in Aging and Alzheimer's Disease." The Center will address several scientific themes including neuroepidemiology of dementia and AD, the boundary between normal aging and AD, and predictors of cognitive impairment in asymptomatic persons. New faculty appointments in Mayo Jacksonville in the basic science of amyloid processing, tau, genetics and antibody development will complement the clinical and epidemiology expertise in the remainder of the Center. Investigators in Scottsdale will add functional imaging studies in at-risk subjects to pursue the scientific themes of the Center. The proposed ADRC will extend the productivity of the existing Alzheimer's Disease Center and develop new insights into aging and AD.